Modified chimeric polypeptides with improved pharmacokinetic properties

Abstract

Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.

1. A fusion protein, consisting of
 a vascular endothelial growth factor (VEGF) receptor component having immunoglobulin-like (Ig) domains consisting of an Ig domain 2 of a first VEGF receptor human Flt1 and an Ig domain 3 of a second VEGF receptor human Flt-4; and 
 a multimerizing component. 
 
     
     
       2. The fusion protein of  claim 1 , wherein the multimerizing component comprises an immunoglobulin domain. 
     
     
       3. The fusion protein of  claim 2 , wherein the immunoglobulin domain is chosen from the Fc domain of IgG and the heavy chain of IgG.